The Study On The Relationship Between Apoptosis-related Gene Bcl-2 And Clinical Biological Behavior Of The Breast Cancer

Objective: As we known, breast cancer, the common malignant tumors,had the highest incidence in the world and seriously threaten the physical and mental health of women. With the development of molecular biology,gene theory about tumorigenesis had been paid widespread attention. During all the associated genes,apoptosis gene shows close relationship with the cause and the development of breast cancer.It had been reported that the relationship of C(-938)A polymorphism in Bcl-2 promoter and the clinical features of breast cancer,such as lymphnode metastases . But there was no report about the relationship of Bcl-2 C(-938)A polymorphism and the canceration of breast cancer.Having detected the genetype of this SNP showed in both breast cancer patients'DNA and the controls',the author aimd at the studying of Bcl-2 C(-938)A polymorphism and made efforts to study the problems: The connection between gene polymorphism and the development of breast cancer; The expression of the genotype and clinical biological behavior of the breast cancer were analyzed principally,while their relationship were summarized;Trying to find out some new items and targets of the development, treatment and prognosis of the breast cancer .Methods: 113 samples of breast cancer patients and 164 samples of health controls were studied to Bcl-2 genetic polymorphism detection, using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP). Clinical data, pathological types, clinical stages, histological grades, the metastatic state of the axillary lymph nodes , estrogen receptor and progestogen receptor of all the breast cancer patients had been sorted to be analyzed.χ2 of SPSS 11.5 statistical package was used to do the statistics analysis. p <0.05 was the size of test.Results:1. The distribution of the Bcl-2 C(-938)A genotypes in 164 healthy controls expected for Hardy-Weinberg equilibrium. There was no obvious difference in the distribution of ages and menopause (χ2=0.302,p=0.67).2. The expression of Bcl-2C(-938)A Polymorphism genotype can be divided into AA genotype, AC genotype and CC genotype. In these cases, the number and percentage of the three genotypes were 40(35.4%), 62(54.9%)and 11(9.7%), while in the control group were 76(46.3%), 69(42.1%)and 19(11.6%). There was no obvious difference in the distribution(χ2=3.292;p=0.070). Bcl-2C(-938)A Polymorphism had no relationship with the risk of breast cancer development, the OR for AC genetype and AA genetype relative to CC genetype in breast cancer were 1.552(95%CI=0.685~3.517) and 0.909(95%CI=0.394~2.096). Between the two groups, the percentage of A allele gene were 62.8% and 67.4%, while C allele gene were 37.2% and 32.6% . There was no obvious difference in the distribution of the two groups(χ2=1.224;p =0.269). Compared with AC+CC genotype, the OR was 0.818(95%CI=0.574~1.167).3. The age distribution of the 113 patients was 20~80, in which the median age was 53. The age distribution of the control group was 19~73, in which the median age was 48. There was no obvious difference in the distribution of the two groups(t=0.906;p =0.366).4. In the case group, there were 64 post-menopause people and 49 pre-menopause people, while in the control group, the number were 107 and 57. There was no obvious difference in the distribution of menstruation condition(χ2=2.098;p =0.148).5. The clinical stage was analyzed. The number and percentage of AA genetype in stage I was 33(70.2%),stage II was 30(65.2%),and stage III was 10(50%), while the AC+CC genetype was 14(29.8%), 16(34.8%)and 10(50%). There was no obvious difference in the distribution of clinical stage(χ2=2.519;p=0.284). Bcl-2C(-938)A Polymorphism had no relationship with clinical stage .Compared with stageⅠ, the OR of stageⅡandⅢwas 1.257(95%CI=0.526~3.004) and 2.357(95%CI=0. 803~6.918).6. The pathological type was analysed. In invasive ductal carcinoma, the number and percentage of AA genotype was 33(38.4%); In invasive lobular carcinoma, it was 2(11.8%); In other types, it was 5(31.3%). When it came to AC+CC genetypes, the percentage was 63(61.6%), 9(81.8%)and 11(68.7%). There was no statistical difference in genotypes distribution(χ2=1.879;p=0.391). Bcl-2C(-938)A Polymorphism had no relationship with pathological type. Compared with invasive lobular carcinoma, the OR of invasive lobular carcinoma and other cancer was 0.357(95%CI=0.073-1.755)and 0.730(95%CI=0.233-2.289).7. The tumor size was analyzed in the 113 pantients. The number and percentage of AA genetype in T≤2cm group was 23(36.5%)in T>2cm group was 17(34.0%)and, while AC+CC genetype was 40(63.5%) and 33(66.0%). There was no obvious difference in the distribution of gentpyes(χ2=0.077;p=0.782). Bcl-2C(-938)A Polymorphism had no relationship with the size of tumor and the OR was 0.891(95%CI=0.411~1.951).8. The number of axillary lymphnode metastases was analyzed. The number and percentage of AA genetype in negative group was 19(26.8%), in positive group was 21(50.0%),while the AC+CC genetype was 52(73.2%) and 21(50.0%). The difference between the two groups was notable. Compared with the AC+CC genotype, AA genotype is relevant with higher lymphnode metastases chance. Take the negative group as reference, The OR of positive group was 2.737(95%CI=1.228-6.098).9. The histological grade was analyzed. The number and percentage of AA genetype in grade I~II group was 29(30.9%), and in grade III group was 11(57.9%), while the AC+CC genetype was 65(69.1%)and 8(42.1%). The difference was notable(χ2=5.055;p=0.025). Compared with AC+CC genetype, the relationship between AA genetype and was related to higher histological grade,and the OR was 3.082(95%CI=1.122~8.465).10. The expression of ER protein was analysed. The number and percentage of AA genetype in ER negative group was 6(24.0%), in ER positive group was 32(40.5%), ER unknown was 7(77.8%);while the AC+CC genetype was 19(76.0%), 47(59.5%) and 2(22.2%). There was no obvious difference between the two groups.(χ2=2.231 ; p=0.135). Bcl-2C(-938)A Polymorphism had no relationship with ER expression. Compared with ER negative group, the OR of positive group was 2.156(95%CI=0.776-5.990)11. The expression of PR protein was analysed. The number and percentage of AA genetype in PR negative group was 8(29.6%), in PR positive group was 30(39.0%), PR unknown was 7(77.8%); while the AC+CC genetype was 19(70.4%), 47(61.0%) and 2(22.2%). There was no obvious difference between the two groups.(χ2=0.751 ; p=0.386). Bcl-2C(-938)A Polymorphism had no relationship with PR expression. Compared with PR negative group, the OR of positive group was 1.516(95%CI=0.589-3.898).12. The expression of C-erb-B2 protein was analysed. The number and percentage of AA genetype in C-erb-B2 negative group was 9(42.9%), in C-erb-B2 positive group was 30(36.1%), C-erb-B2 unknown was 7(77.8%); while the AC+CC genetype was 12(57.1%), 53(63.9%) and 2(22.2%). There was no obvious difference between the two groups.(χ2=0.021 ; p=0.885). Bcl-2C(-938)A Polymorphism had no relationship with C-erb-B2 expression. Compared with C-erb-B2 negative group, the OR of positive group was 0.755(95%CI=0.285-1.998). Conclusion:10. There may be no relationship between the Polymorphism of Bcl-2 C (-938) A and women in northern China get breast cancer.11. The AA genotype of Bcl-2 C (-938) A may be related to higher chance of lymphnode metastases in breast cancer.12. The AA genotype of Bcl-2 C (-938) A may be relevant with higher histological grade of breast cancer.13. There may be no relationship between the Polymorphism of Bcl-2 C (-938) A and clinical stage,pathology type,tumor size,the expression of ER, PR and C-erb-B2 in breast cancer.